The research proposed in the following grant application is aimed at establishing a novel spectroscopic technique to probe solution structures of molecules of biological interest. This new spectroscopic technique is infrared (Vibrational) Circular Dichroism (VCD), which combines principles of vibrational spectroscopy and optical activity. The spectroscopic efforts will center around small molecules which model molecules of biological and biophysical interest. VCD studies have been carried out on peptide fragments and small nucleic acid polymers, establishing VCD as a sensitive probe for solution conformation. In this grant proposal, the further application of VCD to probe the conformation of peptides and nucleotides at local, well-defined positions will be introduced. To permit such a localized probing of molecular conformation, models with distinct vibrational "chromophores" such as isotopic groups will be synthesized. Information about the molecular conformation on such a localized level will further the understanding of the structures and interactions of biomolecules.